AZD9496

Catalog No.S8372 Batch:S837201

Technical Data

Formula	C₂₅H₂₅F₃N₂O₂
Molecular Weight	442.47	CAS No.	1639042-08-2
Solubility (25°C)*	In vitro	DMSO	88 mg/mL (198.88 mM)
		Ethanol	88 mg/mL (198.88 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

AZD9496 is an oral estrogen receptor inhibitor that blocks the growth of ER-positive and ESR1 mutant breast tumours in preclinical models.

Targets

estrogen receptor ^[1]

In vitro

AZD9496 showed pmol/L equipotent binding to both ERα and ERβ isoforms. AZD9496 directly targets ERα for downregulation in vitro. And it also antagonizes and downregulates mutant ER in vitro and in vivo. The IC50s of ERα binding, ERα downregulation, ERα antagonism for AZD9496 are 0.82, 0.14 and 0.28 nM, respectively^[1].

In vivo

AZD9496 showed high oral bioavailability across three species (F% 63, 91, and 74, rat, mouse, and dog, respectively) with generally low volume and clearance across species, albeit a higher clearance in mouse.AZD9496 is a potent, oral inhibitor of breast tumor growth in vivo. AZD9496 causes tumor regressions in combination with PI3K pathway and CDK4/6 inhibitors and in an estrogen-deprived ER+ model of resistance. This effect was accompanied by a dose-dependent decrease in PR protein levels. AZD9496 is currently being evaluated in a phase I clinical trial^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MCF-7 cells Concentrations 100 nM Incubation Time 0, 10, 20, 30, 40, 50 h Method Cells were grown in steroid-free conditions in SILAC media containing 13C615N4 L-arginine to label ERα peptide as "heavy" and then switched to grow in media containing unlabeled l-arginine to label newly synthesized protein as "normal" with 0.1% DMSO, 300 nmol/L tamoxifen, 100 nmol/L AZD9496 for the time indicated.
Animal Study:^{^[1]}	Animal Models Sexually immature female Han Wistar rats Dosages 5 and 25 mg/kg once daily Administration by oral gavage

Cell Assay:^{^[1]}

Cell lines
MCF-7 cells
Concentrations
100 nM
Incubation Time
0, 10, 20, 30, 40, 50 h
Method
Cells were grown in steroid-free conditions in SILAC media containing 13C615N4 L-arginine to label ERα peptide as "heavy" and then switched to grow in media containing unlabeled l-arginine to label newly synthesized protein as "normal" with 0.1% DMSO, 300 nmol/L tamoxifen, 100 nmol/L AZD9496 for the time indicated.

Animal Study:^{^[1]}

Animal Models
Sexually immature female Han Wistar rats
Dosages
5 and 25 mg/kg once daily
Administration
by oral gavage

References

[1] Weir HM, et al. Cancer Res. 2016, 76(11):3307-18.

Customer Product Validation

: , , Onco Targets Ther, 2017, 10: 4809–4819

Selleck's AZD9496 has been cited by 4 publications

SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD), effectively shrinks tumors both in intracranial and subcutaneous ER + breast cancer models [ Breast Cancer Res, 2023, 25(1):96]	PubMed: 37580832
SCR-6852, an oral and highly brain-penetrating estrogen receptor degrader (SERD), effectively shrinks tumors both in intracranial and subcutaneous ER + breast cancer models [ Breast Cancer Res, 2023, 25(1):96]	PubMed: 37580832
G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer. [ Breast Cancer Res Treat, 2020, 10.1007/s10549-020-05575-9]	PubMed: 32130619
low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of rhoa and rac1 [Li S Onco Targets Ther, 2017, 10:4809-4819]	PubMed: 29042792

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.